mCCDcl1 cells show Plasticity Consistent with the Ability to Transition between Principal and Intercalated Cells

The cortical collecting duct of the mammalian kidney plays a critical role in the regulation of body volume, sodium pH, and osmolarity and is composed of two distinct cells types, principal cells and intercalated cells. Each cell type is detectable in the kidney by the localization of specific transport proteins such as aquaporin 2 (Aqp2) and epithelial sodium channel (ENaC) in principal cells and V-ATPase B1 and connexin 30 (Cx30) in intercalated cells. mCCD cl1 cells have been widely used as a mouse principal cell line on the basis of their physiological characteristics. In this study, the mCCD cl1 parental cell line and three sublines cloned from isolated single cells (Ed1, Ed2, and Ed3) were grown on filters to assess their transepithelial resistance, transepithelial voltage, equivalent short circuit current and expression of the cell-specific markers Aqp2, ENaC, V-ATPaseB1, and Cx30. The parental mCCD cl1 cell line presented amiloride-sensitive electrogenic sodium transport indicative of principal cell function; however, immunocytochemistry and RT-PCR showed that some cells expressed the intercalated cell-specific markers V-ATPase B1 and Cx30, including a subset of cells also positive for Aqp2 and ENaC. The three subclonal lines contained cells that were positive for both intercalated and principal cell-specific markers. The vertical transmission of both principal and intercalated cell characteristics via single cell cloning reveals the plasticity of mCCD cl1 cells and a direct lineage relationship between these two physiologically important cell types and is consistent with mCCDcl1 cells being precursor cells. </p

Defining the timing of respiratory syncytial virus (RSV) outbreaks: an epidemiological study

BACKGROUND: Seasonal RSV infections occur every year and affect particularly children under six months of age. Passive immunoprophylaxis with monoclonal antibody Palivizumab is recommended in the period with high risk of RSV infection. This study aims to define the period for the southern part of Germany (Stuttgart area). METHODS: Epidemiological analysis of the RSV situation in southern Germany from 1996 to 2004 and comparison of results with literature was made. The respiratory tract specimens were sent in for the detection of RSV mainly by paediatric clinics. Detection of RSV was carried out mainly by real-time RT-PCR or by ELISA "Pathfinder". RSV outbreaks were depicted as an absolute number and as a percentage of RSV diagnoses in a month. Onsets, offsets, peaks, duration and severity of RSV seasons were defined and analysed. RESULTS: An early season with strong RSV activity (early-high phase) was followed by a weaker late season (late-low phase) in a regular biennial rhythm. However, onsets, offsets and durations of outbreaks varied significantly from year to year. RSV epidemics in southern Germany were found to oscillate in an antiphase with RSV epidemics in Finland and Sweden. CONCLUSION: The long-term regular biennial rhythm allows predicting whether the next outbreak will be late or early and whether RSV activity will be strong or weak. Not foreseeable, however, is the precise time of increase and decrease of RSV activity. Moreover, the regular seasonal pattern may be disrupted by irregular outbreaks. Thus, activity of RSV has to be monitored every year to define the period with high risk of infection

A Quantitative Look at Fluorosis, Fluoride Exposure, and Intake in Children Using a Health Risk Assessment Approach

The prevalence of dental fluorosis in the United States has increased during the last 30 years. In this study, we used a mathematical model commonly employed by the U.S. Environmental Protection Agency to estimate average daily intake of fluoride via all applicable exposure pathways contributing to fluorosis risk for infants and children living in hypothetical fluoridated and non-fluoridated communities. We also estimated hazard quotients for each exposure pathway and hazard indices for exposure conditions representative of central tendency exposure (CTE) and reasonable maximum exposure (RME) conditions. The exposure pathways considered were uptake of fluoride via fluoridated drinking water, beverages, cow’s milk, foods, and fluoride supplements for both age groups. Additionally, consumption of infant formula for infants and inadvertent swallowing of toothpaste while brushing and incidental ingestion of soil for children were also considered. The cumulative daily fluoride intake in fluoridated areas was estimated as 0.20 and 0.11 mg/kg-day for RME and CTE scenarios, respectively, for infants. On the other hand, the RME and CTE estimates for children were 0.23 and 0.06 mg/kg-day, respectively. In areas where municipal water is not fluoridated, our RME and CTE estimates for cumulative daily average intake were, respectively, 0.11 and 0.08 mg/kg-day for infants and 0.21 and 0.06 mg/kg-day for children. Our theoretical estimates are in good agreement with measurement-based estimates reported in the literature. Although CTE estimates were within the optimum range for dental caries prevention, the RME estimates were above the upper tolerable intake limit. This suggests that some children may be at risk for fluorosis

Dysnatremia is a predictor for morbidity and mortality in hospitalized patients with COVID-19

Context: Dysnatremia is an independent predictor of mortality in patients with bacterial pneumonia. There is paucity of data about the incidence and prognostic impact of abnormal sodium concentration in patients with coronavirus disease 2019 (COVID-19). Objective: This work aimed to examine the association of serum sodium during hospitalization with key clinical outcomes, including mortality, need for advanced respiratory support and acute kidney injury (AKI), and to explore the role of serum sodium as a marker of inflammatory response in COVID-19. Methods: This retrospective longitudinal cohort study, including all adult patients who presented with COVID-19 to 2 hospitals in London over an 8-week period, evaluated the association of dysnatremia (serum sodium  145 mmol/L, hyponatremia, and hypernatremia, respectively) at several time points with inpatient mortality, need for advanced ventilatory support, and AKI. Results: The study included 488 patients (median age, 68 years). At presentation, 24.6% of patients were hyponatremic, mainly due to hypovolemia, and 5.3% hypernatremic. Hypernatremia 2 days after admission and exposure to hypernatremia at any time point during hospitalization were associated with a 2.34-fold (95% CI, 1.08-5.05; P = .0014) and 3.05-fold (95% CI, 1.69-5.49; P < .0001) increased risk of death, respectively, compared to normonatremia. Hyponatremia at admission was linked with a 2.18-fold increase in the likelihood of needing ventilatory support (95% CI, 1.34-3.45, P = .0011). Hyponatremia was not a risk factor for in-hospital mortality, except for the subgroup of patients with hypovolemic hyponatremia. Sodium values were not associated with the risk for AKI and length of hospital stay. Conclusion: Abnormal sodium levels during hospitalization are risk factors for poor prognosis, with hypernatremia and hyponatremia being associated with a greater risk of death and respiratory failure, respectively. Serum sodium values could be used for risk stratification in patients with COVID-19

Chondrogenic and Gliogenic Subpopulations of Neural Crest Play Distinct Roles during the Assembly of Epibranchial Ganglia

In vertebrates, the sensory neurons of the epibranchial (EB) ganglia transmit somatosensory signals from the periphery to the CNS. These ganglia are formed during embryogenesis by the convergence and condensation of two distinct populations of precursors: placode-derived neuroblasts and neural crest- (NC) derived glial precursors. In addition to the gliogenic crest, chondrogenic NC migrates into the pharyngeal arches, which lie in close proximity to the EB placodes and ganglia. Here, we examine the respective roles of these two distinct NC-derived populations during development of the EB ganglia using zebrafish morphant and mutants that lack one or both of these NC populations. Our analyses of mutant and morphant zebrafish that exhibit deficiencies in chondrogenic NC at early stages reveal a distinct requirement for this NC subpopulation during early EB ganglion assembly and segmentation. Furthermore, restoration of wildtype chondrogenic NC in one of these mutants, prdm1a, is sufficient to restore ganglion formation, indicating a specific requirement of the chondrogenic NC for EB ganglia assembly. By contrast, analysis of the sox10 mutant, which lacks gliogenic NC, reveals that the initial assembly of ganglia is not affected. However, during later stages of development, EB ganglia are dispersed in the sox10 mutant, suggesting that glia are required to maintain normal EB ganglion morphology. These results highlight novel roles for two subpopulations of NC cells in the formation and maintenance of EB ganglia: chondrogenic NC promotes the early-stage formation of the developing EB ganglia while glial NC is required for the late-stage maintenance of ganglion morphology

Relevance of human metapneumovirus in exacerbations of COPD

BACKGROUND AND METHODS: Human metapneumovirus (hMPV) is a recently discovered respiratory virus associated with bronchiolitis, pneumonia, croup and exacerbations of asthma. Since respiratory viruses are frequently detected in patients with acute exacerbations of COPD (AE-COPD) it was our aim to investigate the frequency of hMPV detection in a prospective cohort of hospitalized patients with AE-COPD compared to patients with stable COPD and to smokers without by means of quantitative real-time RT-PCR. RESULTS: We analysed nasal lavage and induced sputum of 130 patients with AE-COPD, 65 patients with stable COPD and 34 smokers without COPD. HMPV was detected in 3/130 (2.3%) AE-COPD patients with a mean of 6.5 × 10(5 )viral copies/ml in nasal lavage and 1.88 × 10(5 )viral copies/ml in induced sputum. It was not found in patients with stable COPD or smokers without COPD. CONCLUSION: HMPV is only found in a very small number of patients with AE-COPD. However it should be considered as a further possible viral trigger of AE-COPD because asymptomatic carriage is unlikely

The cost-effectiveness of the WINGS intervention: a program to prevent HIV and sexually transmitted diseases among high-risk urban women

BACKGROUND: We evaluated the cost-effectiveness of the WINGS project, an intervention to prevent HIV and other sexually transmitted diseases among urban women at high risk for sexual acquisition of HIV. METHODS: We used standard methods of cost-effectiveness analysis. We conducted a retrospective analysis of the intervention's cost and we used a simplified model of HIV transmission to estimate the number of HIV infections averted by the intervention. We calculated cost-effectiveness ratios for the complete intervention and for the condom use skills component of the intervention. RESULTS: Under base case assumptions, the intervention prevented an estimated 0.2195 new cases of HIV at a cost of $215,690 per case of HIV averted. When indirect costs of HIV were excluded from the analysis, the intervention's cost-effectiveness ratios were$357,690 per case of HIV averted and $31,851 per quality-adjusted life year (QALY) saved. Under base case assumptions, the condom use skills component of the intervention prevented an estimated 0.1756 HIV infections and was cost-saving. When indirect HIV costs were excluded, the cost-effectiveness ratios for the condom use skills component of the intervention were$97,404 per case of HIV averted and $8,674 per QALY saved. CONCLUSIONS: The WINGS intervention, particularly the two sessions of the intervention which focussed on condom use skills, could be cost-effective in preventing HIV among women

Paediatric Investigators Collaborative Network on Infections in Canada (PICNIC) study of aseptic meningitis

BACKGROUND: The seasonality, clinical and radiographic features and outcome of aseptic meningitis have been described for regional outbreaks but data from a wider geographic area is necessary to delineate the epidemiology of this condition. METHODS: A retrospective chart review was completed of children presenting with aseptic meningitis to eight Canadian pediatric hospitals over a two-year period. RESULTS: There were 233 cases of proven enteroviral (EV) meningitis, 495 cases of clinical aseptic meningitis and 74 cases of possible aseptic meningitis with most cases occurring July to October. Headache, vomiting, meningismus and photophobia were more common in children ≥ 5 years of age, while rash, diarrhea and cough were more common in children < 5 years of age. Pleocytosis was absent in 22.3% of children < 30 days of age with proven EV meningitis. Enterovirus was isolated in cerebrospinal fluid (CSF) from 154 of 389 patients (39.6%) who had viral culture performed, and a nucleic acid amplification test for enterovirus was positive in CSF from 81 of 149 patients (54.3%). Imaging of the head by computerized tomography or magnetic resonance imaging was completed in 96 cases (19.7%) and 24 had abnormal findings that were possibly related to meningitis while none had changes that were definitely related to meningitis. There was minimal morbidity and there were no deaths. CONCLUSION: The clinical presentation of aseptic meningitis varies with the age of the child. Absence of CSF pleocytosis is common in infants < 30 days of age. Enterovirus is the predominant isolate, but no etiologic agent is identified in the majority of cases of aseptic meningitis in Canadian children